The purposes of this study are to investigate bacterial factors of importance in the pathogenesis of infections caused by Gram-negative bacilli and means of enhancing immunity to such infections in man. Prior studies have demonstrated that both active and passive immunization of experimental animals, using an antigen shared by almost all enterobacteria (Re determinant of R strains of S. minnesota), affords significant protection against challenge with heterologous Gram-negative bacilli. Similarly, patients with high titers of antibody to Re experienced shock and a fatal outcome during the course of Gram-negative bacteremia only one-third as often as patients with low titers of antibody to Re. It has also been demonstrated that high titers of IgG, but no IgM, antibody against the patient's infecting organism are also associated with a significant reduction in the frequency of shock and death in bacteremia. The apparent protective effect of antibody to Re is independent of O-specific IgG antibody. Studies of the immunogenicity and toxicity of killed Re bacilli, Re LPS, and deoxycholate treated Re bacilli in animals and a limited number of volunteers have suggested that they are effective immunogens without excessive adverse reactions. Confirmation of the safety and immunogenicity of these preparations in volunteers is proposed as a necessary prelude for the development of a vaccine for Gram-negative bacteremia. Other studies will attempt to evaluate any protective activity of antibody to capsular or K antigens and to evaluate changes in coagulation components, kinins, and fibrinolytic components to the pathogenesis of manifestations of bacteremia. BIBLIOGRAPHIC REFERENCES: McCabe, W. R., Johns, M. A., Zinner, S. H. and Greely, A. "Lipopolysaccharides and Protection against Gram-Negative Bacterial Infections" in The Role of Immunological Factors in Infectious, Allergic, and Autoimmune Processes" (Beers, R. F., Jr. and Basset, E. G., Eds.), Raven Press, New York, 1976. Zinner, S. H. and McCabe, W. R. "Effects of IgM and IgG in Patients with Bacteremia Due to Gram-Negative Bacilli" J. Inf. Dis. 133:37-45, 1976.